Skip to main content
SpringerLink
Log in

Demyelinating Cholinesterase Inhibitors: Lipid and Protein Metabolism

  • Chapter
Alterations of Chemical Equilibrium in the Nervous System

  • 154 Accesses

Abstract

Organophosphorus compounds (OPC) are known to cause a specific secondary type of demyelination in nervous tissues: lesions in the axis cylinder and myelin sheath, both in the central nervous system and the peripheral nervous system, have been described, as a result of their neurotoxic action.(1–5) To our knowledge, no review or recent monograph has appeared, dealing with the effects brought about by demyelinating OPC on protein and lipid metabolism of CNS and PNS. Some contributions in this field have, however, appeared in these last years, partially covering this subject matter.(4,6–10) Therefore, I have concentrated mostly on this problem and have tried to collect the most relevant and recent literature in the specific field. As is known, the economic importance of the OPC as insecticides is remarkable.(11,12) A detailed and adequate study of their toxicity and metabolism also is of interest, but this aspect will not be particularly reviewed in this paper.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. M. I. Smith and R. D. Lillie, The histopathology of tri-orthocresyl phosphate poisoning, Arch. Neurol. Psychiatr. (Chicago) 26:976–992 (1931).

    Article  Google Scholar 

  2. J. M. Barnes and F. A. Denz, Experimental demyelination with organo-phosphorus compounds, J. Path Bact. 65:597–605 (1953).

    Article  PubMed  CAS  Google Scholar 

  3. J. B. Cavanagh, The toxic effects of tri-ortho-cresylphosphate on the nervous system. An experimental study in hens, J. Neurol. Neurosurg. Psychiatr. 17:163–172 (1954).

    Article  PubMed  CAS  Google Scholar 

  4. G. Majno and M. L. Karnovsky, A biochemical and morphological study of myelination and demyelination. III. Effect of an organophosphorus compound (mipafox) on the biosynthesis of lipids by nervous tissue of rats and hens, J. Neurochem. 8:1–16 (1961).

    Article  PubMed  CAS  Google Scholar 

  5. C. W. M. Adams (ed.), Neurohistochemistry, Elsevier, Amsterdam (1965).

    Google Scholar 

  6. G. Porcellati, in Protides of the Biological Fluids (H. Peeters, ed.), Vol. 13, pp. 115–126, Elsevier, Amsterdam (1966).

    Google Scholar 

  7. G. Porcellati, The effect of organophosphorus compounds on nerve phospholipid metabolism, Progr. Biochem. Pharmacol. 3:49–58 (1967).

    CAS  Google Scholar 

  8. G. Porcellati, in Third International Symposium on Drugs Affecting Lipid Metabolism (W. H. Holmes, L. A. Carlson, and R. Paoletti, eds.), Advances in Experimental Medicine and Biology Vol. 4, pp. 295–306, Plenum Press, New York (1969).

    Google Scholar 

  9. G. B. Ansell, in Advances in Lipid Research (R. Paoletti and D. Kritchevsky, eds.), Vol. 3, pp. 139–171, Academic Press, New York (1965).

    Google Scholar 

  10. C. D. Joel, H. W. Moser, G. Majno, and M. L. Karnovsky, Effects of bis(mono-isopropylamino)fluoro-phosphine oxide (mipafox) and of starvation on the lipids in the nervous system of the hen, J. Neurochem. 14:479–488 (1967).

    Article  PubMed  CAS  Google Scholar 

  11. D. F. Heath, Organophosphorus Poisons, Pergamon Press, Oxford (1961).

    Google Scholar 

  12. R. D. O’Brien, Toxic Phosphorus Esters, Academic Press, New York (1960).

    Google Scholar 

  13. S. Harris, Jr., Jamaica ginger paralysis (peripheral polyneuritis), Sth. med. J. (Bgham, Ala) 23:375–380 (1930).

    Article  Google Scholar 

  14. P. Glees, Experimentelle Markscheidendegeneration durch Tri-ortho-kresyl Phosphat und ihre Verhütung durch Cortisonacetat, Dtsch. Med. Wschr. 86:1175–1178 (1961).

    Article  PubMed  CAS  Google Scholar 

  15. H. H. Janzik and P. Glees, Chromatolysing spinal neurons in the chick following tricresylphosphate (TCP) intoxication, Acta Neuropath. 6:303–306 (1966).

    Article  PubMed  CAS  Google Scholar 

  16. A. N. Davison, Some observations on the cholinesterases of the central nervous system after the administration of the organophosphorus compounds, Brit. J. Pharmacol. 8:212–216 (1953).

    PubMed  CAS  Google Scholar 

  17. M. C. Lancaster, A note on the demyelination produced in hens by dialkyfluoridates, Brit. J. Pharmacol. 15:279–281 (1960).

    PubMed  CAS  Google Scholar 

  18. J. B. Cavanagh, Peripheral nerve changes in ortho-cresyl phosphate poisoning in the cat, J. Path. Bact. 87:365–383 (1964).

    Article  PubMed  CAS  Google Scholar 

  19. R. L. Baron and J. E. Casida, Enzymatic and antidotal studies on the neurotoxic effect of certain organophosphates, Biochem. Pharmacol. 11:1129–1136 (1962).

    Article  PubMed  CAS  Google Scholar 

  20. M. Eto, J. E. Casida, and T. Eto, Hydroxylation and cyclization reactions involved in the metabolism of TOCP, Biochem. Pharmacol. 11:337–342 (1962).

    Article  PubMed  CAS  Google Scholar 

  21. R. L. Baron and H. Johnson, Neurological disruption produced in hens by two organophosphate esters, Brit. J. Pharmacol. 23:295–304 (1964).

    PubMed  CAS  Google Scholar 

  22. W. N. Aldridge and J. M. Barnes, Further observations on the neurotoxicity of organophosphorus compounds, Biochem. Pharmacol. 15:541–548 (1966).

    Article  PubMed  CAS  Google Scholar 

  23. R. F. Witter and T. B. Graines, Relationship between depression of brain or plasma Cholinesterase and paralysis in chickens caused by certain organic phosphorus compounds, Biochem. Phamacol. 12:1377–1386 (1963).

    Article  CAS  Google Scholar 

  24. D. J. Ecobichon and W. Kalow, Action of organophosphorus compounds upon esterases of human liver, Can. J. Biochem. Physiol. 41:1537–1546 (1963).

    Article  CAS  Google Scholar 

  25. J. D. Taylor, A neurotoxic syndrome produced in cats by a cyclic phosphate metabolite of tri-o-cresyl phosphate, Toxicol. Appl. Pharmacol. 11:538–546 (1967).

    Article  PubMed  CAS  Google Scholar 

  26. D. Hausen, E. Schaum, and O. Wassermann, Distribution and metabolism of DFP in the guinea-pig, Arch. für Toxikol. 23:73–81 (1968).

    Article  Google Scholar 

  27. D. K. Myers, J. B. J. Rebel, C. Veeger, A. Kemp, and E. G. L. Simons, Metabolism of triaryl phosphates in rodents, Nature (London) 176:260–262 (1955).

    Article  Google Scholar 

  28. P. Glees and W. G. White, A study of skin absorption effects of tri-ortho-cresyl phosphate (TOCP) in hens, J. Physiol. (London) 153:20P–22P (1960).

    Google Scholar 

  29. P. Glees and H. H. Janzik, Chemically (TCP) induced fibre degeneration in the central nervous system, with reference to clinical and neuropharmacological aspects, Progr. Brain Res. 14:97–121 (1965).

    Article  CAS  Google Scholar 

  30. A. Bischoff, The ultrastructure of tri-ortho-cresyl phosphate-poisoning. I. Studies on myelin and axonal alterations in the sciatic nerve, Acta Neuropath. 9:158–174 (1967).

    Article  Google Scholar 

  31. J. B. Cavanagh and G. N. Patangia, Changes in the central nervous system in the cat as the result of tri-o-cresyl phosphate poisoning, Brain 88:165–180 (1965).

    Article  PubMed  CAS  Google Scholar 

  32. G. Porcellati, A. Millo, and I. Manocchio, Proteinase activity of nervous tissues in organophosphorus compound poisoning, J. Neurochem. 7:317–320 (1961).

    Article  PubMed  CAS  Google Scholar 

  33. I. Montanini and G. Porcellati, Protein metabolism of peripheral nerves during demyelination by organophosphorus compounds, Ital. J. Biochem. 13:230–239 (1964).

    Google Scholar 

  34. G. Porcellati and M. A. Mastrantonio, Phospholipid metabolism of peripheral nerves during demyelination by organophosphorus compounds, Ital. J. Biochem. 13:332–352 (1964).

    Google Scholar 

  35. L. Illis, G. N. Patangia, and J. B. Cavanagh, Boutons terminaux and tri-ortho-cresyl phosphate neurotoxicity, Exp. Neurol. 14:160–174 (1966).

    Article  PubMed  CAS  Google Scholar 

  36. G. R. Webster, The distribution and metabolism of phosphorus compounds in normal and demyelinating nervous tissue of the chicken, Biochem. J. 57:153–158 (1954).

    PubMed  CAS  Google Scholar 

  37. J. F. Berry and W. H. Cevallos, Lipid class and fatty acid composition of peripheral nerve from normal and organophosphorus-poisoned chickens, J. Neurochem. 13:117–124 (1966).

    Article  PubMed  CAS  Google Scholar 

  38. C. H. Williams, N. J. Johnson, and J. L. Casterline, Cholesterol content of spinal cord and sciatic nerve of hens after organo-phosphate and carbamate administration, J. Neurochem. 13:471–474 (1966).

    Article  PubMed  CAS  Google Scholar 

  39. W. L. Nelson and C. P. Barnum, The effect of diisopropylphosphorofluoridate (DFP) on mouse brain phosphorus metabolism, J. Neurochem. 6:43–49 (1960).

    Article  PubMed  CAS  Google Scholar 

  40. L. Austin, Lipid biosynthesis and chemically induced paralysis in the chicken, Brit. J. Pharmacol. 12:356–360 (1957).

    PubMed  CAS  Google Scholar 

  41. G. Majno and M. L. Karnovsky, Respiration and lipid biosynthesis by rat nerves in vitro, after treatment with a Cholinesterase inhibitor (mipafox), Fed. Proc. 14: 250 (1955).

    Google Scholar 

  42. G. B. Ansell, in Metabolism and Physiological Significance of Lipids (R. M. C. Dawson and D. N. Rhodes, eds.), pp. 481–499, John Wiley, London (1963).

    Google Scholar 

  43. G. B. Ansell and T. Chojnacki, The effect of diisopropylfluorophosphonate on enzymes concerned in brain phospholipid synthesis, Progr. Biochem. Pharmacol. 3:189–195 (1967).

    CAS  Google Scholar 

  44. G. Porcellati, in Convegno Internazionale di Studi sulfa Sclerosi Multipla (C. L. Cazzullo, ed.), pp. 195–206, La Tipografica Varese, Gallarate (1966).

    Google Scholar 

  45. L. E. Hokin, A. Yoda, and R. Sandhu, Irreversible inhibition of adenosine triphosphatases, diglyceride kinase and Phosvitin kinase of brain by diisopropylphos-phorofluoridate, Biochim. Biophys. Acta 126:100–116 (1966).

    Article  PubMed  CAS  Google Scholar 

  46. G. Porcellati, Organofosforici demielinizzanti e lipogenesi del nervo periferico, Acta neurologica 22:168–172 (1967).

    PubMed  CAS  Google Scholar 

  47. J. D. Taylor, The effect of tri-ortho-cresyl phosphate intoxication on phospholipid synthesis in cat spinal cord, Can. J. Physiol. Pharmacol. 43:715–721 (1965).

    Article  CAS  Google Scholar 

  48. C. Ntiforo and M. Stein, Labilization of lysosomes as an aspect of the biochemical toxicology of anticholinesterase pesticides, Biochem. J. 102:44P (1967).

    CAS  Google Scholar 

  49. G. Porcellati, Il metabolismo proteico nella degenerazione e rigenerazione del tessuto nervoso periferico, Farmaco, 20:586–605 (1965).

    CAS  Google Scholar 

  50. D. H. Clouet and H. Waelsch, Amino acid and protein metabolism of the brain. IX. The effect of an organophosphorus inhibitor on the incorporation of 14C-lysine into the proteins of rat brain, J. Neurochem. 10:51–63 (1963).

    Article  PubMed  CAS  Google Scholar 

  51. G. Porcellati, Proteinase activity of nervous tissues during experimental demyelination, Proc. VIIth Intern. Congr. Neurol. 815–822 (1961).

    Google Scholar 

  52. A. Millo and G. Porcellati, The action of some organo-phosphorus compounds on “neutral proteinase” in vitro, Ital. J. Biochem. 10: 333–343 (1961).

    Google Scholar 

  53. G. Porcellati, La reazione fosforilcolinaxitidililtrasferasica nella degenerazione mielinica secondaria, Acta Neurol. 24:119–124 (1969).

    CAS  Google Scholar 

  54. G. Porcellati, in Protein Metabolism of the Nervous System (A. Lajtha, ed.), 601–620, Plenum Press, New York (1970).

    Chapter  Google Scholar 

  55. G. Porcellati, in Handbook of Neurochemistry (A. Lajtha, ed.) Vol. 7, Plenum Press, New York (1971), in press.

    Google Scholar 

  56. G. Porcellati, in Handbook of Neurochemistry (A. Lajtha, ed.) Vol. 2, pp. 393–422, Plenum Press, New York (1969).

    Google Scholar 

  57. B. V. Ramachandran, Distribution of DF32P in mouse organs. III. Incorporation in the brain tissue, Biochem. Pharmacol. 16:1381–1383 (1967).

    Article  PubMed  CAS  Google Scholar 

  58. V. Bonavita and R. Guarneri, NAD- and NADP-linked dehydrogenases in the sciatic nerve of rats injected with di-isopropylfluorophosphonate, Brain Res. 2:200–207 (1966).

    Article  Google Scholar 

  59. R. J. Rossiter, in Chemical Pathology of the Nervous System (J. Folch-Pi, ed.), pp. 207–230, Pergamon Press, London (1961).

    Google Scholar 

  60. J. F. Berry, W. H. Cevallos, and R. R. Wade, Lipid class and fatty acid composition of intact peripheral nerve and during Wallerian degeneration, J. Amer. Oil Chem. Soc. 42:492–500 (1965).

    Article  CAS  Google Scholar 

  61. R. E. McCaman, in Ultrastructure and Metabolism of the Nervous System (S. R. Korey, A. Pope, and E. Robins, eds.), pp. 169–181, Williams and Wilkins, Baltimore (1962).

    Google Scholar 

  62. A. C. Johnson, A. R. McNabb, and R. J. Rossiter, Chemical studies of peripheral nerve during Wallerian degeneration. I. Lipids, Biochem. J. 45:500–508 (1949).

    PubMed  CAS  Google Scholar 

  63. A. C. Johnson, A. R. McNabb, and R. J. Rossiter, Chemistry of Wallerian degeneration. A review of recent studies, Arch. Neurol. Psychiatr. (Chicago) 64:105–121 (1950).

    Article  CAS  Google Scholar 

  64. N. Miani, The relationship between axon and Schwann cell. Phospholipid metabolism of degenerating and regenerating peroneal-tibial nerves of the rabbit in vitro, J. Neurochem. 9:525–536 (1962).

    Article  PubMed  CAS  Google Scholar 

  65. J. Domonkos and L. Heiner, On the possibility of lysophosphatide formation during Wallerian degeneration, J. Neurochem. 15:93–98 (1968).

    Article  PubMed  CAS  Google Scholar 

  66. J. F. Berry and J. D. Coonrad, Hydrolysis of nucleoside diphosphate esters in peripheral nerve during Wallerian degeneration, J. Neurochem. 14:245–255 (1967).

    Article  PubMed  CAS  Google Scholar 

  67. N. Miani, Metabolism and chemical changes in regenerating neurons. III. The rate of incorporation of radioactive phosphate into individual phospholipids of the nerve-cell perikaryon of the C.8 spinal ganglion in vitro, J. Neurochem. 9:537–541 (1962).

    Article  PubMed  CAS  Google Scholar 

  68. D. Nicholls and R. J. Rossiter, Metabolism of lipids of peripheral nerve regenerating after crush, J. Neurochem. 11: 813–818 (1964).

    Article  PubMed  CAS  Google Scholar 

  69. R. J. Rossiter, E. T. Pritchard, and K. P. Strickland, Metabolism of nucleic acids and lipids in brain and in peripheral nerve during experimental demyelination. Neurol. 8; Suppl. 1, 34–40 (1958).

    Google Scholar 

  70. G. Majno and M. L. Karnovsky, A biochemical and morphological study of myelination and demyelination. II. Lipogenesis in vitro by cat nerve following transection. J. Exp. Med. 108:197–214 (1958).

    Article  PubMed  CAS  Google Scholar 

  71. R. E. McCaman, Intermediary metabolism of phospholipids in brain tissue. Micro-determination of choline Phosphokinase, J. Biol. Chem. 237:672–676 (1962).

    Google Scholar 

  72. R. E. McCaman, M. Smith, and K. Cook, Intermediary metabolism of phospholipids in brain tissue. II. Phosphatidic acid phosphatase, J.Biol Chem. 240:3513–3517 (1965).

    PubMed  CAS  Google Scholar 

  73. R. E. McCaman and K. Cook, Intermediary metabolism of phospholipids in brain tissue. III. Phosphocholine-glyceride transferase, J.Biol. Chem. 241:3390–3394 (1966).

    PubMed  CAS  Google Scholar 

  74. G. Porcellati and B. Curti, L’effetto della demiehnizzazione sperimentale sulla attività di alcune fosfatasi dei nervi periferici, Bioch. Appl. 7:42–56 (1960).

    Google Scholar 

  75. M. L. Karnovsky and G. Majno, in Chemical Pathology of the Nervous System (J. Folch-Pi, ed.), pp. 261–266, Pergamon Press, London (1961).

    Google Scholar 

  76. D. F. Matheson and J. B. Cavanagh, Protein synthesis in peripheral nerve and susceptibility to diphtheric neuropathy, Nature (London) 214:721–722 (1967).

    Article  CAS  Google Scholar 

  77. W. N. Aldridge and J. M. Barnes, Esterases and neurotoxicity of some organo-phosphorus compounds, Biochem. Pharmacol. 15:549–554 (1966).

    Article  PubMed  CAS  Google Scholar 

  78. M. K. Johnson, Brain proteins labelled by DFP32 and their connection with the delayed neurotoxic effect of some organophosphorus compounds, First International Congress of Neurochemistry (Strassbourg, 23–28th July, 1967), p. 111.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological, Chemistry University of Pavia, Pavia, Italy

    Giuseppe Porcellati

Authors
  1. Giuseppe Porcellati
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. New York State Research Institute for Neurochemistry and Drug Addiction, Ward’s Island, New York, New York, USA

    Abel Lajtha

Rights and permissions

Reprints and permissions

Copyright information

© 1971 Plenum Press, New York

About this chapter

Cite this chapter

Porcellati, G. (1971). Demyelinating Cholinesterase Inhibitors: Lipid and Protein Metabolism. In: Lajtha, A. (eds) Alterations of Chemical Equilibrium in the Nervous System. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-7175-9_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-7175-9_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-7177-3

  • Online ISBN: 978-1-4615-7175-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation